RHEUMATOID ARTHRITIS (RA)

Autoimmune Rheumatic Disease: Principles of Diagnosis and Treatment

Definition

Epidemiology

• Prevalence: about 1% of population
• Most common age: 40-60 years
• Female:male ratio: ~3:1
• Disability risk: high without timely treatment
• Reduced life expectancy (mainly due to accelerated atherosclerosis and systemic inflammation)

Etiology and Risk Factors

• Genetic predisposition (HLA-DR4, HLA-DR1)
• Immune dysregulation (T and B cell activation)
• Environmental triggers:
  • infections
  • smoking
  • obesity
  • microbiota disturbances
• Hormonal influences

Pathogenesis (Simplified)

1. Immune activation in synovium
2. Cytokine release (TNF-α, IL-1, IL-6)
3. Chronic synovitis and pannus formation
4. Cartilage and bone destruction
5. Joint deformity and loss of function

Clinical Manifestations

Articular

• Morning stiffness (>1 hour)
• Symmetrical small-joint arthritis:
  • MCP, PIP, wrist, MTP joints
• Pain, swelling, warmth, movement limitation
• Typical deformities:
  • “swan neck”
  • “boutonnière”
  • ulnar deviation
  • Z-thumb deformity

Extra-articular

• Rheumatoid nodules
• Fatigue, fever, weight loss
• Vasculitis
• Eye involvement (episcleritis/scleritis)
• Lung involvement (pleuritis, interstitial fibrosis)
• Cardiac involvement (pericarditis, myocarditis)
• Neuropathy, amyloidosis (late/severe)

Diagnosis

Laboratory

• ESR, CRP: elevated
• Rheumatoid factor (RF): often positive
• Anti-CCP (ACCP): high specificity for RA
• CBC: anemia of chronic inflammation, thrombocytosis possible

Imaging

• X-ray/US/MRI:
  • periarticular osteoporosis
  • joint space narrowing
  • erosions
  • subluxations/ankylosis (late stages)

Classification (ACR/EULAR 2010)

• joint involvement
• serology (RF, anti-CCP)
• acute phase reactants (ESR/CRP)
• symptom duration

Disease Activity

• DAS28 index:
  • remission: <2.6
  • low: 2.6-3.2
  • moderate: 3.3-5.1
  • high: >5.1

Treatment Principles

Treat to Target (T2T)

1) NSAIDs

• For pain control only (short-term)

2) Glucocorticoids

• Short-term bridge therapy
• Intra-articular or systemic use when needed

3) Conventional DMARDs (core treatment)

• Methotrexate (gold standard, first line)
• Leflunomide
• Sulfasalazine
• Hydroxychloroquine

4) Biologic/Targeted therapy

• TNF inhibitors (infliximab, adalimumab, etanercept, etc.)
• Rituximab (anti-CD20)
• Tocilizumab (IL-6 receptor blocker)
• Abatacept (T-cell co-stimulation blocker)
• JAK inhibitors (e.g., tofacitinib)

Monitoring

• Regular clinical review + DAS28
• ESR/CRP, CBC, liver and renal function
• Imaging for progression
• Adverse-effect monitoring for DMARDs/biologics

Key Message

1. One-page visual layout format (with colored sections and icons),
2. PowerPoint-ready text blocks, or
3. Printable A3 classroom poster version.

Detailed Classification of Rheumatoid Arthritis (RA)

1) By Serological Variant

A. Seropositive RA (ICD-10 M05)

• M05.0 Felty syndrome
• M05.1 Rheumatoid lung disease
• M05.2 Rheumatoid vasculitis
• M05.3 RA with involvement of other organs/systems
• M05.8 Other seropositive RA
• M05.9 Unspecified seropositive RA

B. Seronegative RA (ICD-10 M06)

• M06.0 Seronegative RA
• M06.1 Adult Still disease
• M06.2 Rheumatoid bursitis
• M06.3 Rheumatoid nodule
• M06.4 Inflammatory polyarthropathy
• M06.8 Other specified RA
• M06.9 Unspecified RA

2) By Clinical Stage (disease duration and structural progression)

A. Very early stage

• Duration: < 6 months
• Symptoms may still be evolving
• Best time for early aggressive therapy

B. Early stage

• Duration: 6 months to 1 year
• “Window of opportunity” for most effective treatment

C. Advanced stage

• Duration: > 1 year
• Typical full clinical picture
• Progressive structural changes; erosions become common

D. Late stage

• Usually ≥ 2 years
• Pronounced destruction/deformity
• Functional limitation and complications more frequent

3) By Disease Activity (DAS28)

• Remission (0): DAS28 < 2.6
• Low activity (1): DAS28 2.6-3.2
• Moderate activity (2): DAS28 3.3-5.1
• High activity (3): DAS28 > 5.1

DAS28 is calculated from:

• Tender joint count (28 joints)
• Swollen joint count (28 joints)
• ESR (or CRP variant)
• Patient global health (VAS)

4) By Structural/Instrumental Type

A. Non-erosive RA

• No erosions on imaging

B. Erosive RA

• Erosions on X-ray/US/MRI

5) By Radiologic Stage (Steinbrocker, modified)

Stage I

• Periarticular osteoporosis
• Minimal/no joint-space narrowing
• No clear erosions or very early changes

Stage II

• Osteoporosis + joint-space narrowing
• Single/early erosions possible
• Mild deformity may begin

Stage III

• Marked osteoporosis and narrowing
• Multiple erosions
• Subluxations and deformities

Stage IV

• Stage III changes + ankylosis
• Severe deformity and structural destruction

6) By Extra-articular/Systemic Manifestations

Without systemic manifestations

With systemic manifestations, such as:

• Rheumatoid nodules
• Cutaneous vasculitis (digital arteritis, nail-bed infarcts, necrotic lesions)
• Neuropathy (mono/polyneuropathy)
• Pleuritis/pericarditis
• Eye involvement (scleritis/episcleritis)
• Sjogren syndrome
• Other organ vasculitis

7) By Anti-citrulline Status

• ACCP positive RA
• ACCP negative RA

• ACCP positivity is linked to more aggressive/erosive course.

8) By Functional Class (FC)

FC I

• Full self-care, work, and non-professional activities preserved

FC II

• Self-care and professional activity preserved
• Non-professional activity limited

FC III

• Self-care preserved
• Professional and non-professional activity significantly limited

FC IV

• Self-care limited
• Professional and non-professional activity markedly restricted

9) By Course Pattern / Progression Rate

• Long spontaneous remission (rare)
• Intermittent course
• Progressive course (most common)
• Rapidly progressive course

10) By Complications

• Secondary amyloidosis
• Secondary osteoarthritis
• Osteoporosis
• Osteonecrosis
• Tunnel syndromes (e.g., carpal tunnel)
• Atlanto-axial instability/subluxation (± myelopathy)
• Accelerated atherosclerosis/cardiovascular risk